Whole Genome Sequencing of Clinical Mycobacterium bovis BCG in Disseminated Infection with Mycotic Aneurysm and ARDS After Intravesical Therapy: A Case Report

Intravesical Bacillus Calmette-Guérin (iBCG) immunotherapy is the standard adjuvant treatment of non-muscle-invasive bladder cancer (NMIBC). Among the potential complications, cases of mycotic aneurysms and acute respiratory distress syndrome (ARDS) are rare but can be life-threatening. Because prior reports have not included whole-genome sequencing (WGS) of clinical <i>Mycobacterium bovis</i> BCG (<i>M. bovis</i> BCG) isolates to assess whether the infecting strain acquires mutations in vivo, we performed WGS in a severe disseminated iBCG-related infection. A 72-year-old man with bladder cancer underwent iBCG instillation. Twelve months after the final instillation, the patient developed an abdominal aortic aneurysm, which was detected and treated with endovascular aneurysm repair (EVAR). Two months later, the patient presented with fever, abdominal pain, and septic shock. Contrast-enhanced computed tomography (CT) and ¹⁸F-fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) showed rapid aneurysm enlargement. Ziehl-Neelsen staining and PCR of aortic material identified <i>M. bovis</i> BCG. Direct PCR on BAL fluid and urine was negative; however, BAL and urine culture subsequently grew <i>M. bovis</i> BCG, and PCR performed on the culture isolate confirmed <i>M. bovis</i> BCG. Despite combined antituberculosis triplet therapy (isoniazid, rifampicin, and ethambutol), the patient developed ARDS, which gradually improved after surgical management. WGS (with >96% genome coverage) showed the isolate was highly concordant with the vaccine strain and lacked additional virulence-associated mutations, including in <i>esxM</i>. This case illustrates that severe systemic iBCG-related complications can occur without detectable in vivo acquisition of virulence-enhancing mutations; however, interpretation is limited by the single-case design and the absence of host genetic susceptibility testing. Our findings underscore the need for prolonged vigilance regarding late-onset vascular and pulmonary complications after iBCG, and highlight the importance of early multidisciplinary management.